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Insulin delivery system

a delivery system and insulin technology, applied in the field of insulin delivery system, can solve the problems of preventing long-term complications, providing tight glycemic regulation, and limiting the clinical application of such systems

Inactive Publication Date: 2006-03-30
GEORGIA TECH RES CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011] Yet another aspect provides a glucose-responsive hydrogel that becomes a sol when in contact with fluid having a glucose concentration of about 25 mM or more, typically of about 27.5 mM or more. The hydrogel can contain pegylated concanavalin A in a ratio of about 2.5 to about 5 PEG:con A. The hydrogel can also include glycogen.

Problems solved by technology

However, this treatment does not provide the tight glycemic regulation afforded by a normally functioning pancreas, thus it cannot prevent long-term complications, which include cardiovascular disease, retinopathy and nephropathy.
However, the clinical application of such systems is still held back by technical difficulties, primarily the in vivo longevity and stability of glucose sensors.
However, as the number of available donors will never meet the large number of patients, and the risk of life-long immunosuppression is of concern, immunologically acceptable insulin-producing cells that exhibit proper secretion dynamics need to be sought.
Due to their autologous nature, such cells relax the immune acceptance challenges, however, their insulin secretion is either constitutive or regulated at the transcriptional level, thus constant or sluggish in response to physiologic stimuli and inadequate for glycemic regulation in higher animals and humans.

Method used

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Examples

Experimental program
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Effect test

example 1

Cell Culture and Transfection

[0081] Autologous non-β cells can be retrieved as a biopsy from a patient. Among non-β cells, hepatocytes and myoblasts are particularly suitable for use as β-cell surrogates. Hepatocytes can be obtained as a biopsy, they express GLUT2 and glucokinase, two major glucose-sensing components in β cells that are involved in regulating insulin secretion, and hepatic expression of insulin under transcriptional regulation has been repeatedly shown to provide some glycemic control in diabetic rodents. However, due to the absence of an acute secretory response, it is unclear that engineered hepatocytes will provide appropriate glycemic regulation in higher animals, without the risk of hypoglycemic episodes. Myoblasts also lack a regulated secretion pathway, but relative to hepatocytes they offer the advantage of easier retrievability as a biopsy, capability in amplifying into large cell number, and the ability for differentiation into stable myotubes. Moreover, ...

example 2

Cell Encapsulation

[0085] To facilitate cell loading into hybrid constructs, βTC3 cells and recombinant HepG2 and C2C12 cells were encapsulated in 2% alginate (ISP Inc., San Diego, Calif.) at a density of 7×107 cells / ml of alginate following the general protocol published by Stabler et al (Stabler et al. 2001), except that a poly-L-lysine membrane and a final alginate coating were not applied. This type of encapsulation does not introduce any significant resistance to the transport of cellular nutrients and metabolites. Briefly, cells from confluent monolayer cultures were detached by EDTA-trypsin (Sigma). A sample of the cell suspension was used for cell counting with trypan blue (Sigma); the rest of the suspension was centrifuged for 4 minutes at 110 g, and pellets were mixed with sodium alginate sterilized by filtration through a 0.2-μm syringe filter (Pall Life Sciences, Ann Arbor, Mich.). Alginate beads of approximately 700 μm diameter were formed by passing the cell-alginate s...

example 3

Characterization of Insulin Release from Constructs

[0086] Each construct was cultured for 20 hours prior to glucose concentration changes to allow insulin to accumulate inside the cell compartment. Two square-waves of glucose were implemented to test the glucose responsiveness of the hybrid construct. Immediately prior to the glucose changes, the culture medium was replaced with fresh, so when an experiment started at t=0, the surrounding medium was insulin-free and contained 25 mM of glucose. Following incubation for 2 hours in this medium, 2.0 g of glucose was directly added to the beaker to increase the glucose concentration to 220 mM. This glucose concentration is necessary to achieve transformation of the con A-based material from gel to sol (Cheng et al. 2004). For the glucose step down 2 hours later, the medium was completely replaced with fresh culture medium containing 25 mM glucose, and the cycle was repeated once more. Although higher than physiologic, use of these gluco...

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Abstract

Aspects of the disclosure generally relate to insulin delivery systems and compositions having a insulin secreting β cell line or insulin secreting recombinant non-β cells sequestered in a glucose-responsive material. The disclosed insulin delivery systems can be surgically implanted in a host and can provide a continuous source of insulin from the cells contained in the device. The combination of living cells with a glucose-responsive material provides a hybrid insulin delivery system that delivers physiologically relevant amounts of insulin in response to physiologically relevant glucose levels. In some aspects, the disclosed devices have a biphasic release of insulin in response to sudden increases in glucose concentrations in the fluids bathing the device.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims priority to and benefit of U.S. Provisional Patent Application No. 60 / 611,544 filed on Sep. 20, 2004, and which is incorporated by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] Aspects of the disclosed work were supported in part by the National Science Foundation under award number EEC-9731643 and by the National Institutes of Health award number DK 56980. Therefore, the US government has certain rights in the disclosed subject matter.BACKGROUND [0003] 1. Technical Field [0004] The disclosed subject matter is generally related to compositions, devices, and systems for regulating physiological responses in a host, in particular medical devices comprising living cells for regulating glucose or insulin levels in a host. [0005] 2. Related Art [0006] Insulin-dependent diabetes is a serious disease affecting more than 3 million people in the US. The current treatment c...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/39A61K38/16
CPCA61K9/0024A61K9/1652A61K38/00A61K35/39A61K9/5052
Inventor SAMBANIS, ATHANASSIOSCHENG, SHING-YI
Owner GEORGIA TECH RES CORP
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